Interleukin 2 (IL-2) has demonstrated a potent ability to augment NK activity and to generate killer cells against NK-insensitive targets and secrete IFN-gamma by LGL. In addition to LGL activity being regulated by a variety of cytokines, LGLs have been shown to produce a variety of lymphokines (IL-1, IFN, CSF, BCGF). A project is being conducted to investigate IFN gene expression and regulation in highly purified human LGLs and T cells. IL-2 treatment of freshly isolated human LGLs rapidly induces IFN-gamma mRNA and protein is secreted in the culture medium. Because of this one signal activation of cytokine genes, the CD3- LGL represents an excellent cell type to study signal transduction leading to both modulations of cytotoxicity and gene transcription, since it represents a cell type "poised" for activation and capable of responding to a single stimulus. Present studies involve examining agents that modulate signal transduction of IL-2 and IFN mediated events, with an emphasis on understanding the mechanism of action of biologicals and defining the specific surface receptors involved.